The human diet has been known for centuries to impact health. For example, gout was determined to be caused by a deficiency in vitamin C which was curable when the diet was modified or supplemented to ensure adequate intake of vitamin C. The use of dietary supplements in the general population is quite common and use of dietary supplements can aid the body in combating diseases while increasing the quality of life of the person taking such supplements.
Inflammation has been associated with a number of disease states and conditions in humans and animals. Two type of inflammation have been recognized in the art-immunogenic inflammation and neurogenic inflammation (also referred to as sterile inflammation since the presence of an infections agent is not required). Immunogenic inflammation arises when an antigen binds to an antibody or leukocyte receptor to trigger an inflammatory cascade. Prior sensitization is required, and the inflammatory response can take several forms including immediate and cell-mediated hypersensitivity. Neurogenic inflammation occurs when an agent triggers the release of inflammatory neuropeptides, such as but not limited to substance P. Neurogenic inflammation can also arise when a nerve impulse travels down an axon to release neurogenic peptides at the terminus. There is an interplay between immunogenic and neurogenic inflammation, in that certain neurogenic peptides can degranulate mast cells, thereby releasing cellular mediators which can activate sensory nerves.
Neurogenic inflammation has been postulated to be involved in a variety of human disease states and conditions, including but not limited to, migraine headache, arthritis, and fibromyalgia. The basis of these conditions may be an acquired neuronal pathway that shunts neurogenic inflammatory stimuli to the cerebral vasculature, joints or muscles, respectively. Migraine headache is a well studied disease in which neurogenic inflammation has been implicated.
According to the National Headache Foundation, one in four households in the United States, or 28 million people, is affected by migraine headaches. Of that total, 11 million people have chronic migraine headaches. Migraine headaches most commonly strike young adult women. The common characteristics are recurrent attacks of headache, with pain occurring most often on one side of the head, accompanied by various combinations of symptoms, such as nausea, vomiting, and sensitivity to light and sound. Migraine headaches can occur at any time of day or night, but occur most frequently occur in the morning. A migraine episode can last from several hours to several days.
Migraine headaches are generally of two types: classic and common. A classic migraine headache is characterized by an “aura” (light spots) or other sensations that are known by the migraineur to occur just prior to the migraine headache itself. A common migraine headache is considered any migraine headache not preceded by an aura or other symptomatic warning to the patient. Migraine headaches are considered a hereditary disease. If both parents have migraine headaches, there is a 75% chance that the offspring will be a “migraineur”; if only one parent has migraine, the chance is as high as 50% that the offspring will be affected.
During a migraine headache, blood vessels in the head go through a cycle of extreme constriction followed by rapid dilation. Nerve pathway changes and imbalances in brain chemistry may cause blood vessels to become inflamed. The interaction between the brain chemistry and blood vessel constriction/dilation is currently debated, but recent research indicates that migraine headaches are caused by alterations in the nerve pathways of the brain, specifically the trigeminal nerve system. When a migraine headache is triggered, the trigeminal nerve releases neuropeptides, such as, but not limited to, substance P and neurotransmitters such as but not limited to serotonin, bradykinin and histamine. These neuropeptides and/or neurotransmitters cause neurogenic inflammation of the brain vasculature and constriction/dilation of the blood vessels which results in migraine pain. Subsequently, trigeminal nerve endings stimulate the release of more neuropeptides and/or neurotransmitters, and a vicious cycle begins. Additionally, altered blood flow affects projections to the visual cortex and visual processing centers that may be associated with the development of aura in many migraine patients.
A variety of causal factors for migraine have been suggested that include, but are not limited to, a deficiency of cerebral magnesium, increased nitric oxide (NO) production and mitochondrial dysfunctions (J Neurol Sci 1995; 134:9). Low cerebral magnesium and/or higher NO production cause platelet aggregation with the subsequent release of serotonin and other neurotransmitters leading to cerebral constriction which may contribute to a migraine attack. Serotonin and other neurotransmitters can also stimulate the release of other pro-inflammatory agents. Furthermore, evidence indicates that impaired mitochondrial energy metabolism in the brain may play a role in the pathology of migraine headaches. Studies indicated that migraine suffers exhibited decreased mitochondrial phosphorylation between migraine attacks, indicating that the mitochondrial energy production was impaired. Specifically, a deficiency in the flavin coenzymes FAD and FMN, which are required by the flavoproteins for efficient mitochondrial electron transport chain, may be implicated in such impaired energy metabolism.
In the past, treatment of migraine has involved non-pharmacologic behavioral modification and physical measures, and pharmacotherapeutic measures. Acute pharmacological drug treatment of migraine may be either to blunt the headache or to reduce the intensity of the attack. Triptans act on serotonin receptors and are currently considered the most important drugs for the acute treatment of migraine. However, when a chronic condition exists characterized by frequent attacks of debilitating pain, a preventive treatment would be desirable. Also, a significant number of patients will benefit from a combined acute and preventative treatment approach.
Preventive medications are usually taken every day in order to reduce the frequency, severity and/or duration of migraine attacks. Patients may prefer such treatments since the frequently recurring migraine significantly interferes with the patients' daily routine. Currently used preventive medications include beta-adrenergic blockers, antidepressants, calcium channel antagonists, serotonin antagonists and anticonvulsants. The doses of the currently used preventative medications required to reduce the frequency of migraine may produce marked and/or intolerable side effects (Goadsby et al. NEJM 2002; 346:260). Therefore, there is a significant need for acute and preventive treatments for migraine suffers and other disease states and conditions associated with neurogenic inflammation that are devoid of said side effects.
The present disclosure provides a composition useful in the treatment and/or prevention of disease states and conditions related to neurogenic inflammation. Furthermore, the present disclosure provides methods of treatment using such compositions. The compositions described are nutritional supplements which are generally recognized as safe for human consumption. Such compositions and methods have heretofore been lacking in the art.